Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System - Summary - MDSpire

Distribution Patterns of Big Tau Isoforms in Human Central and Peripheral Nervous Systems

  • By

  • Rama Krishna Koppisetti

  • Nicolas R. Barthélemy

  • Kanta Horie

  • Cindy V. Ly

  • Kaleigh F. Roberts

  • Srinivas Koutarapu

  • Richard J. Perrin

  • Erin E. Franklin

  • Chiara Pedicone

  • Joshua Orrick

  • Justin Melendez

  • Timothy M. Miller

  • Chihiro Sato

  • Nupur Ghoshal

  • Alison M. Goate

  • Celeste M. Karch

  • Randall J. Bateman

  • Soumya Mukherjee

  • July 19, 2026

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Objective:

To investigate the molecular compositions and anatomic distributions of human big tau isoforms across the nervous system and assess their relevance with aging and neurodegeneration.

Approach:
  • Study Design: Utilized immunoprecipitation-mass spectrometry (IP-MS) to sequence and quantify big tau-specific peptides alongside canonical tau peptides in human nervous system tissues.
  • Sample Collection: Frozen postmortem brain tissue samples from individuals with varying stages of Alzheimer's disease (AD) were obtained for analysis.
Key Findings:
  • First mass spectrometry-based evidence for the translation and expression of the unique tau insertion domain encoded by exon 4a in humans.
  • Defined the molecular diversity and anatomic distribution of big tau in human tissues.
  • Quantified extracellular big tau peptides in cerebrospinal fluid (CSF) from individuals with and without Alzheimer's disease.
Interpretation:

Distinguishing big tau from canonical tau may enhance biomarker strategies for differentiating CNS and PNS neurological diseases.

Limitations:
  • Proteomic evidence for big tau in humans remains limited.
  • The functional rationale for the transition to big tau in specific neuronal populations is not fully understood.
Conclusion:

Findings expand the known repertoire of tau proteins in the human nervous system and suggest potential for improved biomarker strategies.

Original Source(s)

Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System

  • by Rama Krishna Koppisetti, Nicolas R. Barthélemy, Kanta Horie, Cindy V. Ly, Kaleigh F. Roberts, Srinivas Koutarapu, Richard J. Perrin, Erin E. Franklin, Chiara Pedicone, Joshua Orrick, Justin Melendez, Timothy M. Miller, Chihiro Sato, Nupur Ghoshal, Alison M. Goate, Celeste M. Karch, Randall J. Bateman, Soumya Mukherjee

  • July 19, 2026

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